Skip to main content

Advertisement

Log in

Alterations in the gut microbiome in patients with esophageal carcinoma in response to esophagectomy and neoadjuvant treatment

  • Original Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Purpose

Analyzing the gut microbiome is essential for planning treatment strategies to manage esophageal squamous cell carcinoma. This study aimed to characterize the gut microbiome of patients with esophageal squamous cell carcinoma and to identify alterations in its composition during treatment.

Methods

We observed alterations in the gut microbiome in 21 consecutive patients with esophageal squamous cell carcinoma at five different time points, from neoadjuvant treatment to postoperative surgery. Ten healthy individuals were used as a non-cancer control group. Fecal samples were collected and analyzed using 16S ribosomal ribonucleic acid sequencing.

Results

Before treatment, participants with esophageal squamous cell carcinoma had different alpha and beta diversity in comparison to healthy controls. The number of Streptococcus, a facultative anaerobic bacterium, was significantly higher, whereas that of Faecalibacterium, an obligate anaerobic bacterium, was significantly lower. Both alpha and beta diversity remained unchanged during neoadjuvant treatment, but the alterations were pronounced after surgery. The increase in the relative abundance of Streptococcus and the decrease in that of Faecalibacterium also tended to be more pronounced after surgery.

Conclusions

The gut microbiome in patients with esophageal squamous cell carcinoma is altered with surgical intervention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Tachimori Y, Ozawa S, Numasaki H, Ishihara R, Matsubara H, Muro K, et al. Comprehensive registry of esophageal cancer in Japan, 2012. Esophagus. 2019;16:221–45.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Steevens J, Schouten LJ, Goldbohm RA, van den Brandt PA. Alcohol consumption, cigarette smoking and risk of subtypes of oesophageal and gastric cancer: a prospective cohort study. Gut. 2010;59:39–48.

    Article  CAS  PubMed  Google Scholar 

  3. Ishiguro S, Sasazuki S, Inoue M, Kurahashi N, Iwasaki M, Tsugane S, et al. Effect of alcohol consumption, cigarette smoking and flushing response on esophageal cancer risk: a population-based cohort study (JPHC study). Cancer Lett. 2009;275:240–6.

    Article  CAS  PubMed  Google Scholar 

  4. Yachida S, Mizutani S, Shiroma H, Shiba S, Nakajima T, Sakamoto T, et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat Med. 2019;25:968–76.

    Article  CAS  PubMed  Google Scholar 

  5. Peters BA, Wilson M, Moran U, Pavlick A, Izsak A, Wechter T, et al. Relating the gut metagenome and metatranscriptome to immunotherapy responses in melanoma patients. Genome Med. 2019;11:61.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103.

    Article  CAS  PubMed  Google Scholar 

  7. Yao Q, Tang M, Zeng L, Chu Z, Sheng H, Zhang Y, et al. Potential of fecal microbiota for detection and postoperative surveillance of colorectal cancer. BMC Microbiol. 2021;21:156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tomita Y, Ikeda T, Sakata S, Saruwatari K, Sato R, Iyama S, et al. Association of probiotic Clostridium butyricum therapy with survival and response to immune checkpoint blockade in patients with lung cancer. Cancer Immunol Res. 2020;8:1236–42.

    Article  CAS  PubMed  Google Scholar 

  9. Yamamura K, Baba Y, Nakagawa S, Mima K, Miyake K, Nakamura K, et al. Human microbiome Fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin Cancer Res. 2016;22:5574–81.

    Article  CAS  PubMed  Google Scholar 

  10. Yamamura K, Izumi D, Kandimalla R, Sonohara F, Baba Y, Yoshida N, et al. Intratumoral Fusobacterium nucleatum levels predict therapeutic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma. Clin Cancer Res. 2019;25:6170–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Motoori M, Yano M, Miyata H, Sugimura K, Saito T, Omori T, et al. Randomized study of the effect of synbiotics during neoadjuvant chemotherapy on adverse events in esophageal cancer patients. Clin Nutr. 2017;36:93–9.

    Article  PubMed  Google Scholar 

  12. Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Cutsem EV, Piessen G, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384:1191–203.

    Article  CAS  PubMed  Google Scholar 

  13. Deng Y, Tang D, Hou P, Shen W, Li H, Wang T, et al. Dysbiosis of gut microbiota in patients with esophageal cancer. Microb Pathog. 2021;150: 104709.

    Article  CAS  PubMed  Google Scholar 

  14. Kitagawa Y, Uno T, Oyama T, Kato K, Kato H, Kawakubo H, et al. Esophageal cancer practice guidelines 2017 edited by the Japan Esophageal Society: part 1. Esophagus. 2019;16:1–24.

    Article  PubMed  Google Scholar 

  15. Kitagawa Y, Uno T, Oyama T, Kato K, Kato H, Kawakubo H, et al. Esophageal cancer practice guidelines 2017 edited by the Japan esophageal society: part 2. Esophagus. 2019;16:25–43.

    Article  PubMed  Google Scholar 

  16. Matsuki T, Watanabe K, Fujimoto J, Takada T, Tanaka R. Use of 16S rRNA gene-targeted group-specific primers for real-time PCR analysis of predominant bacteria in human feces. Appl Environ Microbiol. 2004;70:7220–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fadrosh DW, Ma B, Gajer P, Sengamalay N, Ott S, Brotman RM, et al. An improved dual-indexing approach for multiplexed 16S rRNA gene sequencing on the Illumina MiSeq platform. Microbiome. 2014;2:6.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Makizaki Y, Uemoto T, Yokota H, Yamamoto M, Tanaka Y, Ohno H. Improvement of loperamide-induced slow transit constipation by Bifidobacterium bifidum G9–1 is mediated by the correction of butyrate production and neurotransmitter profile due to improvement in dysbiosis. PLoS One. 2021;16: e0248584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Japanese Esophageal Society. Japanese classification of esophageal cancer, 11th edition: part I. Esophagus. 2017;14:1–36.

    Article  Google Scholar 

  21. Hazra A, Gogtay N. Biostatistics series module 6: correlation and linear regression. Indian J Dermatol. 2016;61:593–601.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Takagi T, Naito Y, Inoue R, Kashiwagi S, Uchiyama K, Mizushima K, et al. The influence of long-term use of proton pump inhibitors on the gut microbiota: an age-sex-matched case-control study. J Clin Biochem Nutr. 2018;62:100–5.

    Article  CAS  PubMed  Google Scholar 

  23. Allen NE, Beral V, Casabonne D, Kan SW, Reeves GK, Brown A, et al. Moderate alcohol intake and cancer incidence in women. J Natl Cancer Inst. 2009;101:296–305.

    Article  PubMed  Google Scholar 

  24. Abranches J, Zeng L, Kajfasz JK, Palmer SR, Chakraborty B, Wen ZT, et al. Biology of oral Streptococci. Microbiol Spectr. 2018. https://doi.org/10.1128/microbiolspec.GPP3-0042-2018.

    Article  PubMed  Google Scholar 

  25. Palleja A, Kashani A, Allin KH, Nielsen T, Zhang C, Li Y, et al. Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota. Genome Med. 2016;8:67.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ikeda T, Aida M, Yoshida Y, Matsumoto S, Tanaka M, Nakayama J, et al. Alteration in faecal bile acids, gut microbial composition and diversity after laparoscopic sleeve gastrectomy. Br J Surg. 2020;107:1673–85.

    Article  CAS  PubMed  Google Scholar 

  27. Fonseca L, Maliska CM, Cruz MG, Castro L, Gutfilen B. Esophageal reconstruction surgery in oncologic patients: determination of gastric emptying time. J Exp Clin Cancer Res. 2000;19:137–40.

    CAS  PubMed  Google Scholar 

  28. Mori N, Fujita H, Sueyoshi S, Aoyama Y, Yanagawa T, Shirouzu K. Helicobacter pylori infection influences the acidity in the gastric tube as an esophageal substitute after esophagectomy. Dis Esophagus. 2007;20:333–40.

    Article  CAS  PubMed  Google Scholar 

  29. Wu J, Peters BA, Dominianni C, Zhang Y, Pei Z, Yang L, et al. Cigarette smoking and the oral microbiome in a large study of American adults. ISME J. 2016;10:2435–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lopez-Siles M, Duncan SH, Garcia-Gil LJ, Martinez-Medina M. Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics. ISME J. 2017;11:841–52.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bjørkhaug ST, Aanes H, Neupane SP, Bramness JG, Malvik S, Henriksen C, et al. Characterization of gut microbiota composition and functions in patients with chronic alcohol overconsumption. Gut Microbes. 2019;10:663–75.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chaput N, Lepage P, Coutzac C, Soularue E, Roux KL, Monot C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 2017;28:1368–79.

    Article  CAS  PubMed  Google Scholar 

  33. Hibberd AA, Lyra A, Ouwehand AC, Rolny P, Lindegren H, Cedgård L, et al. Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention. BMJ Open Gastroenterol. 2017;4: e000145.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Martini G, Ciardiello D, Dallio M, Famiglietti V, Esposito L, Corte CMD, et al. Gut microbiota correlates with antitumor activity in patients with mCRC and NSCLC treated with cetuximab plus avelumab. Int J Cancer. 2022;151(3):473–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nishijima S, Suda W, Oshima K, Kim SW, Hirose Y, Morita H, et al. The gut microbiome of healthy Japanese and its microbial and functional uniqueness. DNA Res. 2016;23(2):125–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. García-Solache M, Rice LB. The Enterococcus: a model of adaptability to its environment. Clin Microbiol Rev. 2019. https://doi.org/10.1128/CMR.00058-18.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Shi W, Shen L, Zou W, Wang J, Yang J, Wang Y, et al. The gut microbiome is associated with therapeutic responses and toxicities of neoadjuvant chemoradiotherapy in rectal cancer patients-a pilot study. Front Cell Infect Microbiol. 2020;10: 562463.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank all of the participants. We would also like to thank Editage (www.editage.com) for editing the English language of this manuscript. This work was supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI [Grant Number JP20K09035].

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study’s conception and design. HH: collected data and samples and wrote the first draft of the manuscript; YM, HY, YT, and HO: analyzed the gut microbiome data; MS: contributed intellectual inputs, mainly for statistics; HM: collected data and samples; YK: contributed intellectual inputs, mainly for treatment; TI, EO, and TY: supervised the entire study. All authors participated in writing the manuscript and/or critically revising the content. All authors approved the final manuscript.

Corresponding author

Correspondence to Tetsuo Ikeda.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest in association with the present study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hasuda, H., Ikeda, T., Makizaki, Y. et al. Alterations in the gut microbiome in patients with esophageal carcinoma in response to esophagectomy and neoadjuvant treatment. Surg Today 53, 663–674 (2023). https://doi.org/10.1007/s00595-022-02607-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-022-02607-3

Keywords

Navigation